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[PMID]:28260990
[Au] Autor:Byon HJ; Ok SH; Lee SH; Kang S; Cho Y; Han JY; Sohn JT
[Ad] Endere鏾:Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
[Ti] T韙ulo:Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae.
[So] Source:Int J Med Sci;14(2):143-149, 2017.
[Is] ISSN:1449-1907
[Cp] Pa韘 de publica玢o:Australia
[La] Idioma:eng
[Ab] Resumo:The goal of this study was to examine the effect of the alpha-2 adrenoceptor agonist dexmedetomidine on phenylephrine (alpha-1 adrenoceptor agonist)-induced contraction in isolated rat aortae and to elucidate the associated cellular mechanisms, with a particular focus on alpha-1 adrenoceptor antagonism. Dexmedetomidine dose-response curves were generated in isolated endothelium-intact and endothelium-denuded rat aortae precontracted with phenylephrine or 5-hydroxytryptamine. Endothelium-denuded aortic rings were pretreated with either dexmedetomidine or the reversible alpha-1 adrenoceptor antagonist phentolamine, followed by post-treatment with the irreversible alpha-1 adrenoceptor blocker phenoxybenzamine. Control rings were treated with phenoxybenzamine alone. All rings were repeatedly washed with Krebs solution to remove all pretreatment drugs, including phenoxybenzamine, phentolamine and dexmedetomidine. Phenylephrine dose-response curves were then generated. The effect of rauwolscine on the dexmedetomidine-mediated change in phenylephrine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined using western blotting. The magnitude of the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction was higher in endothelium-intact aortae than in endothelium-denuded aortae or endothelium-intact aortae treated with N -nitro-L-arginine methyl ester. However, dexmedetomidine did not significantly alter 5-hydroxytryptamine-induced contraction. In further experiments, prazosin attenuated dexmedetomidine-induced contraction. Additionally, pretreatment with either dexmedetomidine plus phenoxybenzamine or phentolamine plus phenoxybenzamine produced greater phenylephrine-induced contraction than phenoxybenzamine alone, suggesting that dexmedetomidine protects aortae from the alpha-1 adrenoceptor blockade induced by phenoxybenzamine. Rauwolscine attenuated the dexmedetomidine-mediated enhancement of phenylephrine-induced eNOS phosphorylation. Taken together, these results suggest that dexmedetomidine attenuates phenylephrine-induced contractions via alpha-1 adrenoceptor blockade and endothelial nitric oxide release in the isolated rat aorta.
[Mh] Termos MeSH prim醨io: Aorta/efeitos dos f醨macos
Aorta/metabolismo
Dexmedetomidina/farmacologia
觴ido N韙rico/metabolismo
Fenilefrina/farmacologia
Receptores Adren閞gicos/metabolismo
[Mh] Termos MeSH secund醨io: Agonistas Adren閞gicos/farmacologia
Animais
T閏nicas In Vitro
Masculino
Contra玢o Muscular/efeitos dos f醨macos
Fenoxibenzamina/farmacologia
Ratos
Serotonina/farmacologia
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Adrenergic Agonists); 0 (Receptors, Adrenergic); 0TTZ664R7Z (Phenoxybenzamine); 1WS297W6MV (Phenylephrine); 31C4KY9ESH (Nitric Oxide); 333DO1RDJY (Serotonin); 67VB76HONO (Dexmedetomidine)
[Em] M阺 de entrada:1706
[Cu] Atualiza玢o por classe:170627
[Lr] Data 鷏tima revis鉶:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.7150/ijms.17456


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[PMID]:28100576
[Au] Autor:Macrosson D; Love A
[Ad] Endere鏾:North Shore Hospital, Auckland, New Zealand.
[Ti] T韙ulo:Perioperative management of a large, late presenting phaeochromocytoma.
[So] Source:BMJ Case Rep;2017, 2017 Jan 18.
[Is] ISSN:1757-790X
[Cp] Pa韘 de publica玢o:England
[La] Idioma:eng
[Ab] Resumo:A 77-year-old man presenting to the emergency department with an acute coronary syndrome was later found to have a phaeochromocytoma. The lateness of this presentation was likely due to the protective α blocking effects of long-term terazosin therapy for his prostatism. α blockers such as terazosin are a well-recognised medical therapy in the perioperative optimisation of phaeochromocytoma because they treat the adrenergic effects of catecholamine release from the tumour such as hypertension. This patient was diagnosed with an ST elevation myocardial infarction (STEMI). A cardiac angiogram showed no evidence of vessel occlusion. A right adrenal mass of 9󭅍鈥卌m was incidentally found and confirmed as a phaeochromocytoma with raised plasma metanephrines and normetanephrines. Following preoperative optimisation and multidisciplinary team involvement, an open right adrenalectomy was performed successfully some months later.
[Mh] Termos MeSH prim醨io: Neoplasias das Gl鈔dulas Suprarrenais/terapia
Adrenalectomia
Antagonistas Adren閞gicos alfa/uso terap陁tico
Assist阯cia Perioperat髍ia
Fenoxibenzamina/uso terap陁tico
Feocromocitoma/terapia
Infarto do Mioc醨dio com Supradesn韛el do Segmento ST/diagn髎tico
[Mh] Termos MeSH secund醨io: Neoplasias das Gl鈔dulas Suprarrenais/complica珲es
Neoplasias das Gl鈔dulas Suprarrenais/diagn髎tico por imagem
Idoso
Angiografia Coron醨ia
Eletrocardiografia
Seres Humanos
Masculino
Feocromocitoma/complica珲es
Feocromocitoma/diagn髎tico por imagem
Infarto do Mioc醨dio com Supradesn韛el do Segmento ST/etiologia
Tomografia Computadorizada por Raios X
[Pt] Tipo de publica玢o:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Adrenergic alpha-Antagonists); 0TTZ664R7Z (Phenoxybenzamine)
[Em] M阺 de entrada:1703
[Cu] Atualiza玢o por classe:170306
[Lr] Data 鷏tima revis鉶:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE


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[PMID]:27687340
[Au] Autor:Subramaniam A; Grauer R; Beilby D; Tiruvoipati R
[Ad] Endere鏾:Monash University, Clayton, Victoria, Australia; Frankston Hospital, Peninsula Health, Frankston, Victoria, Australia.
[Ti] T韙ulo:Anesthetic management of a myotonic dystrophy patient with paraganglionoma.
[So] Source:J Clin Anesth;34:21-8, 2016 Nov.
[Is] ISSN:1873-4529
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Ab] Resumo:Myotonic dystrophy (DM), though rare, can significantly complicate anesthesia due to muscular and extra-muscular involvement. When this condition is compounded by a pheochromocytoma, anesthetizing such patients becomes extra challenging. We present a case report of a 61-year-old lady with congenital DM, with the whole gamut of associated features, was diagnosed with a noradrenaline secreting paraganglionoma following investigation of refractory hypertension. We anesthetized her for an open resection of the lesion. The conduct of anesthesia and recovery of this patient is described. Our experience suggests that anesthetizing these patients though challenging can be safely managed with relaxant general anesthesia and epidural analgesia with meticulous care pre, intra and post-surgical intervention.
[Mh] Termos MeSH prim醨io: Neoplasias das Gl鈔dulas Suprarrenais/cirurgia
Anestesia Geral/m閠odos
Vasoespasmo Coron醨io/tratamento farmacol骻ico
Hipertens鉶/tratamento farmacol骻ico
Distrofia Miot鬾ica/complica珲es
Paraganglioma/cirurgia
Assist阯cia Perioperat髍ia
Feocromocitoma/cirurgia
[Mh] Termos MeSH secund醨io: Neoplasias das Gl鈔dulas Suprarrenais/complica珲es
Neoplasias das Gl鈔dulas Suprarrenais/diagn髎tico
Antagonistas Adren閞gicos alfa/uso terap陁tico
Antagonistas Adren閞gicos beta/uso terap陁tico
Anestesia Epidural
Anest閟icos Intravenosos/administra玢o & dosagem
Anest閟icos Locais/administra玢o & dosagem
Catecolaminas/sangue
Catecolaminas/urina
Vasoespasmo Coron醨io/etiologia
Vasoespasmo Coron醨io/urina
Feminino
Seres Humanos
Hipertens鉶/etiologia
Hipertens鉶/urina
Meia-Idade
Paraganglioma/complica珲es
Paraganglioma/diagn髎tico
Fenoxibenzamina/uso terap陁tico
Feocromocitoma/complica珲es
Feocromocitoma/diagn髎tico
Propranolol/uso terap陁tico
Tomografia Computadorizada por Raios X
[Pt] Tipo de publica玢o:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Adrenergic alpha-Antagonists); 0 (Adrenergic beta-Antagonists); 0 (Anesthetics, Intravenous); 0 (Anesthetics, Local); 0 (Catecholamines); 0TTZ664R7Z (Phenoxybenzamine); 9Y8NXQ24VQ (Propranolol)
[Em] M阺 de entrada:1707
[Cu] Atualiza玢o por classe:170817
[Lr] Data 鷏tima revis鉶:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161001
[St] Status:MEDLINE


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[PMID]:27461343
[Au] Autor:Berizzi AE; Gentry PR; Rueda P; Den Hoedt S; Sexton PM; Langmead CJ; Christopoulos A
[Ad] Endere鏾:Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
[Ti] T韙ulo:Molecular Mechanisms of Action of M5 Muscarinic Acetylcholine Receptor Allosteric Modulators.
[So] Source:Mol Pharmacol;90(4):427-36, 2016 Oct.
[Is] ISSN:1521-0111
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Ab] Resumo:Recently, the first subtype-selective allosteric modulators of the M5 muscarinic acetylcholine receptor (mAChR) have been described, but their molecular mechanisms of action remain unknown. Using radioligand-binding and functional assays of inositol phosphate (IP) accumulation and Ca(2+) mobilization in a recombinant cell line stably expressing the human M5 mAChR, we investigated the effects of the positive allosteric modulator (PAM), ML380, and negative allosteric modulator, ML375. In functional assays, ML380 caused robust enhancements in the potency of the full agonists, acetylcholine (ACh), carbachol, and oxotremorine-M, while significantly increasing the maximal response to the partial agonist, pilocarpine. ML380 also demonstrated direct allosteric agonist activity. In contrast, ML375 displayed negative cooperativity with each of the agonists in a manner that varied with the pathway investigated and progressively reduced the maximal pilocarpine response. Radioligand-binding affinity cooperativity estimates were consistent with values derived from functional assays in some instances but not others, suggesting additional allosteric effects on orthosteric ligand efficacy. For ML375 this was confirmed in IP assays performed after reduction of receptor reserve by the alkylating agent, phenoxybenzamine, as it reduced the maximal ACh response. In contrast, ML380 enhanced only ACh potency after receptor alkylation, with no effect on maximal response, consistent with studies of the M1 mAChR with the prototypical PAM, BQZ12. Interaction studies between ML380 and ML375 also indicated that they most likely used an overlapping allosteric site. Our findings indicate that novel small-molecule modulators of the M5 mAChR display mixed mechanisms of action compared with previously characterized modulators of other mAChRs.
[Mh] Termos MeSH prim醨io: Imidaz骾s/farmacologia
Indaz骾s/farmacologia
Ind骾s/farmacologia
Receptor Muscar韓ico M5/metabolismo
Sulfonamidas/farmacologia
[Mh] Termos MeSH secund醨io: Acetilcolina/farmacologia
Regula玢o Alost閞ica/efeitos dos f醨macos
S韙io Alost閞ico/efeitos dos f醨macos
Animais
Atropina/farmacologia
C閘ulas CHO
Cricetinae
Cricetulus
Seres Humanos
Imidaz骾s/qu韒ica
Indaz骾s/qu韒ica
Ind骾s/qu韒ica
Fosfatos de Inositol/metabolismo
Fenoxibenzamina/farmacologia
Ensaio Radioligante
Sulfonamidas/qu韒ica
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (1-((1H-Indazol-5-yl)sulfonyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide); 0 (9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo(2,1-a)isoindol-5(9bH)-one); 0 (Imidazoles); 0 (Indazoles); 0 (Indoles); 0 (Inositol Phosphates); 0 (Receptor, Muscarinic M5); 0 (Sulfonamides); 0TTZ664R7Z (Phenoxybenzamine); 7C0697DR9I (Atropine); N9YNS0M02X (Acetylcholine)
[Em] M阺 de entrada:1705
[Cu] Atualiza玢o por classe:170501
[Lr] Data 鷏tima revis鉶:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160728
[St] Status:MEDLINE
[do] DOI:10.1124/mol.116.104182


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[PMID]:26643509
[Au] Autor:Ramachandran R; Rewari V
[Ad] Endere鏾:Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, Delhi, India. rashmiramachandran1@gmail.com.
[Ti] T韙ulo:Preoperative optimization in pheochromocytoma: phenoxybenzamine may be redundant but not alpha blockade.
[So] Source:Can J Anaesth;63(5):629, 2016 May.
[Is] ISSN:1496-8975
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Mh] Termos MeSH prim醨io: Fenoxibenzamina
Feocromocitoma/cirurgia
[Mh] Termos MeSH secund醨io: Neoplasias das Gl鈔dulas Suprarrenais/cirurgia
Seres Humanos
Hipertens鉶
Cuidados Pr-Operat髍ios
[Pt] Tipo de publica玢o:COMMENT; LETTER
[Nm] Nome de subst鈔cia:
0TTZ664R7Z (Phenoxybenzamine)
[Em] M阺 de entrada:1608
[Cu] Atualiza玢o por classe:160403
[Lr] Data 鷏tima revis鉶:
160403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151209
[St] Status:MEDLINE
[do] DOI:10.1007/s12630-015-0557-y


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[PMID]:26409450
[Au] Autor:Lin XB; Jiang L; Ding MH; Chen ZH; Bao Y; Chen Y; Sun W; Zhang CR; Hu HK; Cai Z; Lu CY; Zhou JY; Qian J; Wu XJ; Jin WL; Hu GH
[Ad] Endere鏾:Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
[Ti] T韙ulo:Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.
[So] Source:Tumour Biol;37(3):2901-8, 2016 Mar.
[Is] ISSN:1423-0380
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Ab] Resumo:Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.
[Mh] Termos MeSH prim醨io: Antineopl醩icos/farmacologia
Glioma/tratamento farmacol骻ico
Fenoxibenzamina/farmacologia
[Mh] Termos MeSH secund醨io: Animais
Linhagem Celular Tumoral
Movimento Celular
Prolifera玢o Celular
Glioma/patologia
Seres Humanos
Prote韓as de Membrana/an醠ise
Camundongos
Invasividade Neopl醩ica
Prote韓as do Tecido Nervoso/an醠ise
Fenoxibenzamina/uso terap陁tico
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Antineoplastic Agents); 0 (LINGO1 protein, human); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0TTZ664R7Z (Phenoxybenzamine)
[Em] M阺 de entrada:1702
[Cu] Atualiza玢o por classe:171111
[Lr] Data 鷏tima revis鉶:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150928
[St] Status:MEDLINE
[do] DOI:10.1007/s13277-015-4102-y


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[PMID]:26440247
[Au] Autor:Sambhunath D; Pankaj K; Usha K
[Ad] Endere鏾:Department of Cardiac Anaesthesia, All India Institute of Medical Sciences, New Delhi, India.
[Ti] T韙ulo:Role of phenoxybenzamine in perioperative clinical practice.
[So] Source:Ann Card Anaesth;18(4):577-8, 2015 Oct-Dec.
[Is] ISSN:0974-5181
[Cp] Pa韘 de publica玢o:India
[La] Idioma:eng
[Mh] Termos MeSH prim醨io: Agonistas alfa-Adren閞gicos/uso terap陁tico
Procedimentos Cir鷕gicos Card韆cos
Hipotens鉶/tratamento farmacol骻ico
Assist阯cia Perioperat髍ia/m閠odos
Fenoxibenzamina/uso terap陁tico
Taquicardia/tratamento farmacol骻ico
[Mh] Termos MeSH secund醨io: Seres Humanos
[Pt] Tipo de publica玢o:LETTER
[Nm] Nome de subst鈔cia:
0 (Adrenergic alpha-Agonists); 0TTZ664R7Z (Phenoxybenzamine)
[Em] M阺 de entrada:1607
[Cu] Atualiza玢o por classe:170220
[Lr] Data 鷏tima revis鉶:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151007
[St] Status:MEDLINE
[do] DOI:10.4103/0971-9784.166473


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[PMID]:26010736
[Au] Autor:Romero M; Kapur G; Baracco R; Valentini RP; Mattoo TK; Jain A
[Ad] Endere鏾:Division of Nephrology and Hypertension, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.
[Ti] T韙ulo:Treatment of Hypertension in Children With Catecholamine-Secreting Tumors: A Systematic Approach.
[So] Source:J Clin Hypertens (Greenwich);17(9):720-5, 2015 Sep.
[Is] ISSN:1751-7176
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Ab] Resumo:Management of blood pressure in children with pheochromocytoma and other catecholamine-secreting tumors (CSTs) is unique and challenging. The authors report a single-center experience using sequential α-adrenergic blockade (phenoxybenzamine), increased fluid intake, and -blockade for presurgical management of 10 CSTs in children. In this retrospective review, mean duration for blood pressure control in preparation for surgery was 4.52.6爓eeks. Intraoperative hypertension was noted transiently (<2爃ours) in eight patients (80%) and was treated with continuous infusion of short-acting antihypertensive agents. Two (20%) patients required vasopressor medication infusion to manage intraoperative hypotension. Only two (20%) patients developed postoperative hypotension and required vasopressor medication infusion for<24爃ours. All antihypertensive medications were discontinued in the immediate (≤4燿ays) postoperative period in 80% of patients. In conclusion, a systematic and multidisciplinary approach utilizing adrenergic blockade is effective in treating children with CSTs.
[Mh] Termos MeSH prim醨io: Antagonistas Adren閞gicos alfa/uso terap陁tico
Anti-Hipertensivos/uso terap陁tico
Press鉶 Sangu韓ea/fisiologia
Catecolaminas/secre玢o
Hipertens鉶/complica珲es
Hipertens鉶/tratamento farmacol骻ico
Hipotens鉶/tratamento farmacol骻ico
Fenoxibenzamina/uso terap陁tico
Feocromocitoma/complica珲es
Feocromocitoma/cirurgia
[Mh] Termos MeSH secund醨io: Adolescente
Neoplasias das Gl鈔dulas Suprarrenais/cirurgia
Press鉶 Sangu韓ea/efeitos dos f醨macos
Catecolaminas/sangue
Catecolaminas/metabolismo
Crian鏰
Pr-Escolar
Feminino
Seres Humanos
Hipotens鉶/complica珲es
Lactente
Per韔do Intraoperat髍io
Masculino
Feocromocitoma/patologia
Feocromocitoma/secre玢o
Per韔do P髎-Operat髍io
Estudos Retrospectivos
Resultado do Tratamento
Prote韓a Supressora de Tumor Von Hippel-Lindau/metabolismo
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Adrenergic alpha-Antagonists); 0 (Antihypertensive Agents); 0 (Catecholamines); 0TTZ664R7Z (Phenoxybenzamine); EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein); EC 6.3.2.- (VHL protein, human)
[Em] M阺 de entrada:1607
[Cu] Atualiza玢o por classe:161125
[Lr] Data 鷏tima revis鉶:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150527
[St] Status:MEDLINE
[do] DOI:10.1111/jch.12571


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[PMID]:25837937
[Au] Autor:Omori Y; Nakajima M; Nishimura K; Takahashi E; Arai T; Akahira M; Suzuki T; Kainoh M
[Ad] Endere鏾:Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Yu_Omori@nts.toray.co.jp.
[Ti] T韙ulo:Analgesic effect of GT-0198, a structurally novel glycine transporter 2 inhibitor, in a mouse model of neuropathic pain.
[So] Source:J Pharmacol Sci;127(3):377-81, 2015 Mar.
[Is] ISSN:1347-8648
[Cp] Pa韘 de publica玢o:Japan
[La] Idioma:eng
[Ab] Resumo:This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of glycine transporter 2 (GlyT2) in human GlyT2-expressing HEK293 cells and did not bind various major transporters or receptors of neurotransmitters in a competitive manner. Thus, GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. Intravenous, oral, and intrathecal injections of GT-0198 decreased the pain-related response in a model of neuropathic pain with partial sciatic nerve ligation. This result suggests that GT-0198 has an analgesic effect. The analgesic effect of GT-0198 was abolished by the intrathecal injection of strychnine, a glycine receptor antagonist. Therefore, GT-0198 is considered to exhibit its analgesic effect via the activation of a glycine receptor by glycine following presynaptic GlyT2 inhibition in the spinal cord. In summary, GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in爒ivo efficacy in behavioral models of neuropathic pain.
[Mh] Termos MeSH prim醨io: Analg閟icos
Benzamidas/administra玢o & dosagem
Benzamidas/farmacologia
Prote韓as da Membrana Plasm醫ica de Transporte de Glicina/antagonistas & inibidores
Neuralgia/tratamento farmacol骻ico
Piperidinas/administra玢o & dosagem
Piperidinas/farmacologia
[Mh] Termos MeSH secund醨io: Animais
Benzamidas/antagonistas & inibidores
Benzamidas/qu韒ica
Modelos Animais de Doen鏰s
C閘ulas HEK293
Seres Humanos
Ligadura
Masculino
Camundongos Endog鈓icos ICR
Fenoxibenzamina
Piperidinas/antagonistas & inibidores
Piperidinas/qu韒ica
Nervo Isqui醫ico
Medula Espinal
Estricnina/farmacologia
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Analgesics); 0 (Benzamides); 0 (GT-0198); 0 (Glycine Plasma Membrane Transport Proteins); 0 (Piperidines); 0TTZ664R7Z (Phenoxybenzamine); H9Y79VD43J (Strychnine)
[Em] M阺 de entrada:1604
[Cu] Atualiza玢o por classe:150403
[Lr] Data 鷏tima revis鉶:
150403
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150404
[St] Status:MEDLINE


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[PMID]:25822781
[Au] Autor:Livingstone M; Duttchen K; Thompson J; Sunderani Z; Hawboldt G; Sarah Rose M; Pasieka J
[Ad] Endere鏾:University of Calgary, 1403 - 29 Street NW, Calgary, AB, T2N 2T9, Canada. Meggie.livingstone@albertahealthservices.ca.
[Ti] T韙ulo:Hemodynamic Stability During Pheochromocytoma Resection: Lessons Learned Over the Last Two Decades.
[So] Source:Ann Surg Oncol;22(13):4175-80, 2015 Dec.
[Is] ISSN:1534-4681
[Cp] Pa韘 de publica玢o:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ideal perioperative management of pheochromocytomas/paragangliomas (pheo) is a subject of debate and can be highly variable. The purpose of this study was to identify potential predictive factors of hemodynamic instability during pheo resection. METHODS: A retrospective review of pheo resections from 1992 to 2013 was undertaken. Intraoperative hemodynamics, patient demographics, tumor characteristics, and perioperative management were examined. Postoperative intensive-care admission, myocardial infarction, stroke, and 30-day mortality were reviewed. Linear regression was used to analyze factors influencing intraoperative hemodynamics. RESULTS: During the 20-year study period, 100 patients underwent pheo resection. Postoperative morbidity and mortality was significantly reduced (p = 0.003) in the last 10 years of practice, and there was a trend towards greater morbidity and mortality with intraoperative hemodynamic instability (p = 0.06). The preoperative dose of phenoxybenzamine and the number of laparoscopic procedures has increased in the last decade [59 mg (95 % CI 32-108) to 106 mg (95 % CI 91-124), p = 0.008, and 27 vs. 54 %, p = 0.05, respectively]. Increased preoperative phenoxybenzamine dose was a significant predictor of improved intraoperative hemodynamic stability (p = 0.01). Lack of intraoperative magnesium use resulted in greater hemodynamic instability as preoperative systolic blood pressure increased (p = 0.002). CONCLUSIONS: Postoperative outcomes following pheo resection have improved over the last two decades. Preoperative α-blockade plays a significant role in improving intraoperative hemodynamics and post-op outcomes. Increased doses of phenoxybenzamine and utilization of laparoscopic approaches have likely contributed to improved outcomes in the last decade. Intraoperative magnesium use may provide protection against hemodynamic instability and warrants further study.
[Mh] Termos MeSH prim醨io: Neoplasias das Gl鈔dulas Suprarrenais/cirurgia
Adrenalectomia
Hemodin鈓ica
Feocromocitoma/cirurgia
[Mh] Termos MeSH secund醨io: Neoplasias das Gl鈔dulas Suprarrenais/mortalidade
Neoplasias das Gl鈔dulas Suprarrenais/fisiopatologia
Antagonistas Adren閞gicos alfa/administra玢o & dosagem
Adulto
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Monitoriza玢o Intraoperat髍ia
Estadiamento de Neoplasias
Fenoxibenzamina/administra玢o & dosagem
Feocromocitoma/mortalidade
Feocromocitoma/fisiopatologia
Complica珲es P髎-Operat髍ias
Progn髎tico
Estudos Retrospectivos
Fatores de Risco
Taxa de Sobrevida
[Pt] Tipo de publica玢o:JOURNAL ARTICLE
[Nm] Nome de subst鈔cia:
0 (Adrenergic alpha-Antagonists); 0TTZ664R7Z (Phenoxybenzamine)
[Em] M阺 de entrada:1609
[Cu] Atualiza玢o por classe:151114
[Lr] Data 鷏tima revis鉶:
151114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150331
[St] Status:MEDLINE
[do] DOI:10.1245/s10434-015-4519-y



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